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Updated: Jun 2, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Click Peptide concept: o-acyl isopeptide of islet amyloid polypeptide as a nonaggregative precursor molecule
Taku Yoshiya1, Ayano Higa, Naoko Abe
1Kyoto Pharmaceutical University, Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Yamashina-ku, Kyoto, Japan.
Abstract:
The O-acyl isopeptide (1) of islet amyloid polypeptide (IAPP), which contains an ester moiety at both Ala8-Thr9 and Ser19-Ser20, was prepared by sequential segment condensation based on the O-acyl isopeptide method. Isopeptide 1 possessed nonaggregative properties, retaining its random coil structure under the acidic conditions; this suggests that the insertion of the O-acyl isopeptide structures in IAPP suppressed aggregation of the molecule. As a result of the rapid O-to-N acyl shift of 1 under neutral pH, in situ-formed IAPP adopted a random-coil structure at the start of the experiment, and then underwent conformational change to α-helix/β-sheet mixed structures as well as aggregation. The click peptide strategy with the nonaggregative precursor molecule 1 could be a useful experimental tool to identify the functions of IAPP, by overcoming the handling difficulties that arise from IAPP's intense and uncontrollable self-assembling nature.
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